2030. The world hovers on the brink of World War IV. Kaneda, once leader of a delinquent gang, is caught up in the aftermath of a power struggle between a Japanese military research organization--led by a man known only as the Colonel--and a resistance group whose members include Kay, Ryu, and a formidable woman named Chiyoko.
The Colonel has a number of psychic children under his control. Each is identified by a number marked on the hand. Among them are Kiyoko and Masaru--Numbers 25 and 27. The blind Lady Miyako--Number 19--was once among their ranks but now heads a great religious cult. Number 41 is Tetsuo, once Kaneda's friend but now his greatest enemy. Tetsuo lost an arm to a laser blast from the Colonel's military satellite SOL and has used cybernetics and telekinesis to fabricate for himself a prosthetic left arm.
Most powerful of all the children is Number 28--Akira--a docile and enigmatic boy who was placed in cryogenic sleep forty years ago, after he started the Third World War with a mental blast. He was recently reawakened by the jealous and ambitious Tetsuo. Shortly thereafter, he responded to emotional trauma by again devastating the reconstructed city of Neo-Tokyo. Japan now exists in a state of emergency. The forces of the army and the resistance are scattered and the military's formidable "caretaker robots" patrol the streets.
In the western part of Neo-Tokyo, the Great Tokyo Empire is formed--a monarchy with Akira on the throne and Tetsuo as his prime minister. Together the pair use their powers, healing the sick, wielding control of the faithful, and organizing their subjects into fighting units to defend their land. To increase the empire's power, Tetsuo uses drugs to develop psychic abilities in some of his subjects. Most faithful among their numerous followers is Tetsuo's aide who is determined at all costs to destroy Lady Miyako, who offers sanctuary to any who come to her eastern shrine.
The Empire is infiltrated by teams of spies from the outside world, but all of them except Lieutenant Yamada--who takes temporary shelter with Ryu--are killed. Ryu wants to join Yamada, and Tetsuo meets the pair and reveals that Yamada has come to kill Akira. The spy decides to separate from Ryu and go his own way.
The Colonel is wounded and living in hiding with one of his scientists. He believes Tetsuo could become another Akira, and is determined to kill Tetsuo to atone for what he has brought about. However, military forces outside Neo-Tokyo are trying by computer to wrestle control of SOL from him. At this same time, Tetsuo, acting upon advice from Lady Miyako, is trying to master his own weaknesses so that he can master Akira.
Meanwhile, Lady Miyako, Masaru and Kiyoko try to convince Kay to join them in the battle against Tetsuo. Although Kay lacks native psychic abilities, she is a powerful medium through whom others can project their powers and strike as one. Lady Miyako explains that Akira's personality has been destroyed by his power, leaving him in a passive vessel, and that when Tetsuo's character is likewise eroded, he too will be beyond control. Kay considers Tetsuo's most recent action--destroying part of the moon and setting off geological cataclysms on earth merely to impress his and Akira's followers--and she agrees to be purified and join the others. Following his huge expenditure of power--which leaves many dead, and Ryu buried alive--Tetsuo begins to lose control, and his artificial arm assumes a grossly mutated form.
Aboard an American naval vessel, an international conclave of scientists studying the Akira phenomenon--which they've code-named Juvenile A--are aghast to learn that, despite their recommendations, the world's armies have amassed an Akira Assassination Corps and are even more upset by the knowledge that the young and dedicated soldiers are sure to be slaughtered by the inconceivable might of their enemy. The Admiral commanding the ship scoffs when the scientists tell him that Tetsuo has teleported aboard to taunt his "fan club", refusing to be convinced even by the telekinetic havoc, death and injury the boy left in his wake.
Kaneda, who's teamed up with Kai and Joker--a friend and rival from his gang days--is outraged to learn of the risk Miyako has talked Kay into taking. He vows to kill Tetsuo himself rather than let her face such danger. Then, at long last, he kisses Kay and promises her that they'll spend the night together when they next meet.
Emperor Akira mercifully sleeps, but the limitations of an increasingly barely human body wear on Tetsuo, the power within eager to escape his flesh. Ragged American troops begin what passes for an assault on the city of Neo-Tokyo, as duplicitous scientists, pushed to the edge, scheme agendas to undo the powerful forces in motion. And below the rubble, a desparate Kaneda and Joker arm themselves for a war they have no hope of winning and no way of avoiding.
The madness that passes for day-to-day in the Great Tokyo Empire has begun to take its toll on all... bringing each that much closer to the breaking point...